新生大鼠早产儿脑白质损伤的多模态磁共振成像评估及机制探讨

doi:10.7499/j.issn.1008-8830.2411071

摘要
图/表
参考文献(14)
相关文章 (15)
点击分布统计
下载分布统计

全文: PDF (2918 KB) [HTML]
输出: BibTeX | EndNote (RIS) 背景资料

摘要目的基于多模态磁共振成像（magnetic resonance imaging, MRI）结合组织学评估新生大鼠早产儿脑白质损伤（preterm white matter injury, PWMI）并探讨其机制。方法将健康3日龄Sprague-Dawley新生大鼠随机分为假手术组与PWMI组（各组n=12）。通过缺氧、缺血法建立新生大鼠PWMI模型。采用激光散斑成像技术观察建模后不同时间点新生大鼠脑血氧饱和度及血流量变化，采用多模态MRI观察脑白质损伤情况，苏木精-伊红染色观察损伤侧纹状体区形态学变化，免疫荧光染色检测少突胶质祖细胞的增殖及分化。结果建模后0、6、12、24、72 h，PWMI组损伤侧相对血流量和相对血氧饱和度均低于假手术组（P<0.05）。建模后24 h，PWMI组损伤侧脑白质可见T2加权成像呈高信号，相对表观扩散系数值、洛伦兹差分值均低于假手术组（P<0.001）；PWMI组神经细胞排列紊乱，EdU⁺PDGFR-α⁺细胞数高于假手术组（P<0.001）。建模后28 d，PWMI组脑白质区相对各向异性分数值、EdU⁺Olig2⁺细胞数以及髓鞘碱性蛋白、神经丝蛋白200荧光强度均低于假手术组（P<0.001）。结论多模态MRI可活体评估新生大鼠PWMI模型早、远期PWMI变化，为新生儿PWMI诊疗提供影像学和病理学依据；缺氧缺血可抑制新生大鼠少突胶质细胞祖细胞的增殖与分化，导致PWMI。

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	高啸天
	张海默
	张孝祖
	王怡静
	毕惠宁
	于淼
	李艳
	王晓莉

关键词 ：早产儿脑白质损伤, 多模态磁共振成像, 少突胶质祖细胞, 新生大鼠

Abstract：Objective To evaluate preterm white matter injury (PWMI) in neonatal rats using multimodal magnetic resonance imaging (MRI) combined with histological assessments and to explore its underlying mechanisms. Methods Healthy 3-day-old Sprague-Dawley neonatal rats were randomly divided into a sham operation group and a PWMI group (n=12 in each group). A PWMI model was established in neonatal rats through hypoxia-ischemia. Laser speckle imaging was used to observe changes in cerebral oxygen saturation and blood flow at different time points post-modeling. Multimodal MRI was employed to assess the condition of white matter injury, while hematoxylin-eosin staining was utilized to observe morphological changes in the striatal area on the injured side. Immunofluorescence staining was performed to detect the proliferation and differentiation of oligodendrocyte precursor cells. Results At 0, 6, 12, 24, and 72 hours post-modeling, the relative blood flow and relative oxygen saturation on the injured side in the PWMI group were significantly lower than those in the sham operation group (P<0.05). At 24 hours post-modeling, T2-weighted imaging showed high signals in the white matter of the injured side in the PWMI group, with relative apparent diffusion coefficient values and Lorenz differential values being lower than those in the sham operation group (P<0.001); additionally, the arrangement of nerve cells in the PWMI group was disordered, and the number of EdU⁺PDGFR-α⁺ cells was higher than that in the sham operation group (P<0.001). At 28 days post-modeling, the relative fractional anisotropy values, the number of EdU⁺Olig2⁺ cells, and the fluorescence intensity of myelin basic protein and neurofilament protein 200 in the white matter region of the PWMI group were all lower than those in the sham operation group (P<0.001). Conclusions Multimodal MRI can evaluate early and long-term changes in PWMI in neonatal rat models in vivo, providing both imaging and pathological evidence for the diagnosis and treatment of PWMI in neonates. Hypoxia-ischemia inhibits the proliferation and differentiation of oligodendrocyte precursor cells in neonatal rats, leading to PWMI.

Key words： Preterm white matter injury Multimodal magnetic resonance imaging Oligodendrocyte precursor cell Neonatal rat

收稿日期: 2024-11-13

基金资助:国家自然科学基金（82071888）；山东省自然科学基金（ZR2024MH067）；2019年高等学校青创人才引育计划；潍坊市科学技术发展计划项目（2021GX058）。

通讯作者: 王晓莉，女，教授。Email：wxlpine@163.com。 E-mail: wxlpine@163.com

作者简介: 高啸天，男，硕士研究生；

引用本文:

高啸天,张海默,张孝祖等. 新生大鼠早产儿脑白质损伤的多模态磁共振成像评估及机制探讨[J]. 中国当代儿科杂志, 2025, 27(3): 366-372.

GAO Xiao-Tian,ZHANG Hai-Mo,ZHANG Xiao-Zu et al. Multi-modal magnetic resonance imaging assessment and mechanism exploration of preterm white matter injury in neonatal rats[J]. CJCP, 2025, 27(3): 366-372.

链接本文:

http://www.zgddek.com/CN/10.7499/j.issn.1008-8830.2411071 或 http://www.zgddek.com/CN/Y2025/V27/I3/366

	Cayam-Rand D, Guo T, Synnes A, et al. Interaction between preterm white matter injury and childhood thalamic growth[J]. Ann Neurol, 2021, 90(4): 584-594. PMID: 34436793. DOI: 10.1002/ana.26201.
	Zhu Z, Yuan L, Wang J, et al. Mortality and morbidity of infants born extremely preterm at tertiary medical centers in China from 2010 to 2019[J]. JAMA Netw Open, 2021, 4(5): e219382. PMID: 33974055. PMCID: PMC8114138. DOI: 10.1001/jamanetworkopen.2021.9382.
	Vaes JEG, Brandt MJV, Wanders N, et al. The impact of trophic and immunomodulatory factors on oligodendrocyte maturation: potential treatments for encephalopathy of prematurity[J]. Glia, 2021, 69(6): 1311-1340. PMID: 33595855. PMCID: PMC8246971. DOI: 10.1002/glia.23939.
	Jablonska B, Adams KL, Kratimenos P, et al. Sirt2 promotes white matter oligodendrogenesis during development and in models of neonatal hypoxia[J]. Nat Commun, 2022, 13(1): 4771. PMID: 35970992. PMCID: PMC9378658. DOI: 10.1038/s41467-022-32462-2.
	Vannucci RC, Vannucci SJ. A model of perinatal hypoxic-ischemic brain damage[J]. Ann N Y Acad Sci, 1997, 835: 234-449. PMID: 9616778. DOI: 10.1111/j.1749-6632.1997.tb48634.x.
	Ohshima M, Tsuji M, Taguchi A, et al. Cerebral blood flow during reperfusion predicts later brain damage in a mouse and a rat model of neonatal hypoxic-ischemic encephalopathy[J]. Exp Neurol, 2012, 233(1): 481-489. PMID: 22143064. DOI: 10.1016/j.expneurol.2011.11.025.
	Liu C, Wang C, Zhang H, et al. Hypoxia ischemia results in blood brain barrier damage via AKT/GSK-3β/CREB pathway in neonatal rats[J]. Brain Res, 2024, 1822: 148640. PMID: 37863169. DOI: 10.1016/j.brainres.2023.148640.
	Li Z, Gong P, Zhang M, et al. Multi-parametric MRI assessment of melatonin regulating the polarization of microglia in rats after cerebral ischemia/reperfusion injury[J]. Brain Res Bull, 2023, 204: 110807. PMID: 37923146. DOI: 10.1016/j.brainresbull.2023.110807.
	Bartley J, Soltau T, Wimborne H, et al. BrdU-positive cells in the neonatal mouse hippocampus following hypoxic-ischemic brain injury[J]. BMC Neurosci, 2005, 6: 15. PMID: 15743533. PMCID: PMC555560. DOI: 10.1186/1471-2202-6-15.
	Shin JE, Lee H, Jung K, et al. Cellular response of ventricular-subventricular neural progenitor/stem cells to neonatal hypoxic-ischemic brain injury and their enhanced neurogenesis[J]. Yonsei Med J, 2020, 61(6): 492-505. PMID: 32469173. PMCID: PMC7256006. DOI: 10.3349/ymj.2020.61.6.492.
	Msayib Y, Harston GWJ, Tee YK, et al. Quantitative CEST imaging of amide proton transfer in acute ischaemic stroke[J]. Neuroimage Clin, 2019, 23: 101833. PMID: 31063943. PMCID: PMC6503165. DOI: 10.1016/j.nicl.2019.101833.
	Lai JHC, Liu J, Yang T, et al. Chemical exchange saturation transfer magnetic resonance imaging for longitudinal assessment of intracerebral hemorrhage and deferoxamine treatment at 3T in a mouse model[J]. Stroke, 2023, 54(1): 255-264. PMID: 36416125. DOI: 10.1161/STROKEAHA.122.040830.
	Cui J, Afzal A, Zu Z. Comparative evaluation of polynomial and Lorentzian lineshape-fitted amine CEST imaging in acute ischemic stroke[J]. Magn Reson Med, 2022, 87(2): 837-849. PMID: 34590729. PMCID: PMC9293005. DOI: 10.1002/mrm.29030.
	Lin Q, Lin L, Li L, et al. Dynamic changes of oligodendrogenesis in neonatal rats with hypoxic-ischemic white matter injury[J]. Brain Res, 2023, 1817: 148495. PMID: 37481153. DOI:10.1016/j.brainres.2023.148495.